Sensitization of pelvic afferent nerves in the in vitro rat urinary bladder-pelvic nerve preparation by purinergic agonists and cyclophosphamide pretreatment

Yu, Yongbei; Groat, William C. de

doi:10.1152/ajprenal.00592.2007

Cited by 78 publications

(96 citation statements)

References 44 publications

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“…Cystitis induced by cyclophosphamide pretreatment can mimic the sensitizing effect of purinergic agonists, consistent with the evidence that ATP is involved in nociceptive mechanisms in the urinary bladder [747]. Subsensitivity of P2X3 and P2X2/3 receptors, but not vanilloid receptors, has been shown in L6-S1 DRG in the rat model of cyclophosphamide cystitis [79].…”

Section: Detrusor Overactivitysupporting

confidence: 80%

Purinergic signalling in the urinary tract in health and disease

Burnstock

2013

Purinergic Signalling

140

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Purinergic signalling is involved in a number of physiological and pathophysiological activities in the lower urinary tract. In the bladder of laboratory animals there is parasympathetic excitatory cotransmission with the purinergic and cholinergic components being approximately equal, acting via P2X1 and muscarinic receptors, respectively. Purinergic mechanosensory transduction occurs where ATP, released from urothelial cells during distension of bladder and ureter, acts on P2X3 and P2X2/3 receptors on suburothelial sensory nerves to initiate the voiding reflex, via low threshold fibres, and nociception, via high threshold fibres. In human bladder t h e p u r i n e rg i c c o m p o n e n t o f p a r a s y m p a t h e t i c cotransmission is less than 3 %, but in pathological conditions, such as interstitial cystitis, obstructed and neuropathic bladder, the purinergic component is increased to 40 %. Other pathological conditions of the bladder have been shown to involve purinoceptor-mediated activities, including multiple sclerosis, ischaemia, diabetes, cancer and bacterial infections. In the ureter, P2X7 receptors have been implicated in inflammation and fibrosis. Purinergic therapeutic strategies are being explored that hopefully will be developed and bring benefit and relief to many patients with urinary tract disorders.

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Section: Detrusor Overactivitysupporting

confidence: 80%

Purinergic signalling in the urinary tract in health and disease

Burnstock

2013

Purinergic Signalling

140

149

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“…Thus, it is possible that activation of bladder nerves and urothelial cells can modulate bladder function directly or indirectly via the release of chemical factors in the urothelial layer. ATP released from the urothelium facilitates stretch induced bladder afferent firing in cyclophosphamide irritated bladders but does not have a detectable effect in normal bladders, indicating that the role of ATP is unregulated in pathological conditions (726). ATP released from the urothelium or surrounding tissues may also regulate membrane trafficking in urothelial cells.…”

Section: Peripheral Nervous Systemmentioning

confidence: 99%

Neural Control of the Lower Urinary Tract

Groat

Griffiths

Yoshimura

2014

Comprehensive Physiology

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527

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This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

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“…Various NNRs are expressed in the urothelium (Beckel et al, 2006) and stimulation of urothelial α3 NNR with cytisine releases ATP (Beckel and Birder, 2012) which has an excitatory effect on bladder afferents (Ralevic and Burnstock, 1998; Yu and de Groat, 2008). In anesthetized rats intravesical administration of cytisine facilitates reflex micturition, an effect suppressed by PPADS, a purinergic receptor antagonist, suggesting that activation of NNRs near the lumenal surface of the bladder sensitizes afferents in part via an indirect purinergic mechanism (Beckel et al, 2006; Beckel and Birder, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Standard electrophysiological methods were used to amplify and analyze the afferent nerve activity (Yu and de Groat, 2008). Afferent firing was elicited by intravesical infusion of Krebs solution at the rate of 0.04 ml/min for 8 min which also evoked rhythmic contractions of the bladder smooth muscle.…”

Section: Methodsmentioning

confidence: 99%

“…In the present experiments we used an in vitro bladder-pelvic afferent nerve preparation (Yu and de Groat, 2008) to examine the effects of nicotinic receptor agonists (epibatidine or nicotine) and antagonists (mecamylamine or hexamethonium) on the activity of mechano-sensitive bladder afferents induced by bladder distension. The results indicate that activation of nicotinic receptors enhances the activity of mechano-sensitive afferents with receptors near the urothelium, inhibits the activity of mechano-sensitive afferents with receptors at other sites in the bladder and excites unidentified afferent nerves.…”

Section: Introductionmentioning

confidence: 99%

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Effects of nicotinic receptor agonists on bladder afferent nerve activity in an in vitro bladder–pelvic nerve preparation

Daugherty

Groat

2016

Brain Research

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Effects of nicotinic receptor agonists (epibatidine and nicotine) on mechano-sensitive bladder afferent nerve (MS-BAN) activity were studied in an in vitro bladder-pelvic afferent nerve preparation. MS-BAN activity was induced by isotonic distention of the bladder at pressures of 10–40 cmH2O. The effect of epibatidine varied according to the concentration, route of administration and the intravesical pressure stimulus. Epibatidine (300–500 nM) administered in the perfusate to the serosal surface of the bladder decreased distension evoked afferent firing by 30%–50% depending on the bladder pressure. However these concentrations also produced an immediate increase in tonic afferent firing in the empty bladder. Lower concentrations (50–100 nM) elicited weaker and more variable effects. The inhibitory effects were blocked by bath application of mecamylamine (150 μM) a nicotinic receptor antagonist. Bath application of nicotine (20 μM) elicited similar effects. Intravesical administration of epibatidine (500 nM) significantly increased MS-BAN firing by 15–30%; while lower concentrations (200–300 nM) were ineffective. This facilitatory effect of epibatidine was blocked by intravesical administration of mecamylamine (250 μM). Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. Bath application of epibatidine (300 nM) or nicotine (20 μM) did not change either the voltage threshold or the area of evoked AP. These results indicate that nicotinic agonists: (1) enhance MS-BAN activity originating at afferent receptors near the urothelium, (2) inhibit MS-BAN activity originating at afferent receptors located at other sites in the bladder, (3) directly excite unidentified afferents, (4) do not alter afferent axonal excitability.

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Sensitization of pelvic afferent nerves in the in vitro rat urinary bladder-pelvic nerve preparation by purinergic agonists and cyclophosphamide pretreatment

Cited by 78 publications

References 44 publications

Purinergic signalling in the urinary tract in health and disease

Purinergic signalling in the urinary tract in health and disease

Neural Control of the Lower Urinary Tract

Effects of nicotinic receptor agonists on bladder afferent nerve activity in an in vitro bladder–pelvic nerve preparation

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